This work is investigating several aspects of pancreatic islet transplantation in animals. During the past year we have demonstrated that neonatal rat islets can be stored at 4 degrees C for four days and at minus 196 degrees C for at least one month and ameliorate diabetes after transplantation. Histological studies have demonstrated that all islet cell types survive in the liver of rats after transplantation. Islet transplantation experiments have shown that hypertriglyceridemia can be reversed in diabetic rats, that virally induced diabetes in mice can be reversed by islet transplantation, that adenosine deaminase inhibitors can have a moderate effect on islet allograft survival in mice and rats, and that approximately 50% of the pancreatic islet tissue that is transplanted to the liver survives. In the coming year, we will investigate the effect of DL-ethionine treatment of the donor pancreas on the preparation of islet tissue for transplantation in dogs. We will also define the influence of immunosuppressive regimens used to prevent islet allograft rejection on glucose metabolism. Our goals in preservation are to store adult islet tissue at 4 degrees C and in the frozen state. We will also investigate new ways of preparing dispersed pancreatic tissue for transplantation, including a discontinuous collagenase digestion technique without screen filtration. For allograft experiments, we will investigate the influence of adenosine deaminase inhibitors, cyclosporin, niridazole and other agents on prolonging allograft survival in diabetic rats, mice and dogs. The effect of correction of diabetes on immune defects in diabetic mice will also be investigated.